Mahner 2017.

Study name	Role of neoadjuvant chemotherapy in advanced ovarian cancer: TRUST‐trial of radical upfront surgical therapy in advanced ovarian cancer (ENGOT ov33 / AGO‐OVAR OP7)
Methods	Multi‐centre international randomised controlled trial comparing primary debulking surgery (maximally debulked ‐ complete gross resection) followed by 6 cycles of chemotherapy (control arm) with 3 cycles of neoadjuvant chemotherapy followed by interval debulking surgery (maximally debulked ‐ complete gross resection) and another 3 cycles of chemotherapy (experimental arm). There are 3 parts to the trial the first 2 parts were conducted in Germany alone. The 3rd part is the multi‐centre international trial including centres in the UK (1), USA (1), France (3), Germany (8), Italy (3), Denmark (1), Austria (1) and Sweden (2). All are actively recruiting at present except Austria. The trial aims to recruit 686 participants
Participants	Suspected or histologically‐confirmed, newly diagnosed invasive epithelial ovarian cancer FIGO stage IIIB‐IV (IV only if resectable metastasis) Females aged ≥ 18 years Women who have given their written informed consent Good performance status (ECOG 0/1) Good ASA score (1/2) Preoperative CA 125/CEA ratio ≥ 25 (if CA‐125 is elevated)* If < 25 and/or biopsy with non‐serous, non‐endometrioid histology, esophago‐gastro‐duodenoscopy (EGD) and colonoscopy mandatory to exclude gastrointestinal primary cancer Assessment of an experienced surgeon, that is based on all available information, the women can undergo the procedure and the tumour can potentially be completely resected Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. This ANC cannot have been induced or supported by granulocyte colony stimulating factors. Platelet count ≥ 100 x 109/L. Renal function: Serum‐Creatinine ≤ 1.5 x institutional upper limit normal (ULN). Hepatic function: Bilirubin ≤ 1.5 x ULN. SGOT ≤ 3 x ULN Alkaline phosphatase ≤ 2.5 x ULN. Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE Grade 1
Interventions	Primary debulking surgery followed by 6 cycles of chemotherapy (control arm) or 3 cycles of neoadjuvant chemotherapy followed by interval debulking surgery and a further 3 cycles of chemotherapy (experimental arm)
Outcomes	Primary outcome measure is OS (Women will be followed up for a minimum of 5 years after registration/randomisation or until death) Secondary outcome measures are: Progression‐free survival (PFS) (Women will be followed up for a minimum of 5 years after registration/randomisation or until death) Progression‐free survival time is calculated from the date of randomisation until the date of first progressive disease or death, whichever occurs first or date of last contact (censored observation). Progressive disease is defined as clinical or imaging‐detected tumour progression or death in cases without prior documented tumour progression. Progression‐free survival 2 (PFS2) (Women will be followed up for a minimum of 5 years after registration/randomisation or until death) PFS2 time is calculated from the date of randomisation until the date of second progressive disease or death, whichever occurs first or date of last contact (censored observation). Time to first subsequent anticancer therapy or death (TFST) (Time Frame: Women will be followed up for a minimum of 5 years after registration/randomisation or until death) Time to first subsequent anticancer therapy is calculated from the date of randomisation until the starting date of the first subsequent anticancer therapy or death, whichever occurs first or date of last contact (censored observation). Maintenance treatments following a cytostatic treatment are not considered separate treatment lines. Time to second subsequent anticancer therapy or death (TSST) (Time frame: Women will be followed up for a minimum of 5 years after registration/randomisation or until death) Time to second subsequent anticancer therapy is calculated from the date of randomisation until the starting date of the second subsequent anticancer therapy or death, whichever occurs first or date of last contact (censored observation). Maintenance treatments following a cytostatic treatment are not considered separate treatment lines. QoL (Time frame: women will be followed up for a minimum of 5 years after registration/randomisation or until death) QoL as measured by EORTC QLQ‐C30 (Version 3), EORTC QLQ‐OV28, EQ‐5D‐3L Documentation of surgical complications (Time frame: women will be followed up for 1 year after surgery or until death) Assessment of safety: documentation of surgical complications 28 days after surgery and 1 year after surgery.
Starting date	Recruitment commenced in July 2016 and is expected to close in April 2023.
Contact information	office‐wiesbaden@ago‐ovar.de
Notes